Potential health effects of drinking water disinfection by-products using quantitative structure toxicity relationship

Disinfection by-products (DBPs) are produced as a result of disinfecting water using various treatment methods. Over the years, chlorine has remained the most popular disinfecting agent due to its ability to kill pathogens. However, in 1974, it was discovered that the superchlorination of drinking water resulted in the production of chloroform and other trihalomethanes. Since then hundreds of additional DBPs have been identified, including haloacetic acids and haloacetonitriles with very little or no toxicological data available, thus necessitating the use of additional methods for hazard estimation. Quantitative Structure Toxicity Relationship (QSTR) is one such method and utilizes a computer-based technology to predict the toxicity of a chemical solely from its molecular attributes. The current research was conducted utilizing the TOPKAT®/QSTR software package which is comprised of robust, cross-validated QSTR models for assessing mutagenicity, rodent carcinogenicity (female/male; rat/mouse), developmental toxicity, skin sensitization, lowest-observed-adverse-effect level (LOAEL), fathead minnow LC 50, rat oral LD 50 and Daphia magna EC 50. A total of 252 DBPs were analyzed for the likelihood that they would produce tumors and developmental effects using the carcinogenicity and developmental toxicity submodels of TOPKAT®. The model predictions were evaluated to identify generalizations between the functional groups (e.g. alcohols, acids, etc.) and specific toxic endpoints. Developmental toxicity was identified as an endpoint common to the majority of aliphatic mono- and dicarboxylic acids, aliphatic halogenated and non-halogenated ketones, and aliphatic haloacetonitriles. In the case of the carcinogenicity submodels, most aliphatic aldehydes were identified as carcinogens only in the female mouse submodel. The majority of the aliphatic and aromatic dicarboxylic acids were identified as carcinogens in the female rat submodel. All other functional groups examined were largely predicted as non-carcinogens in all the cancer submodels (i.e. male/female rats and mice). The QSTR results should aid in the prioritization for evaluation of toxic endpoints in the absence of in vivo bioassays.